The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

I can only imagine the author intended to write "Dampen" rather than "Damper"!!! (How is it that others are paid for writing this mess and I am not???? Hmmmm....) At any rate, data already theoretically supporting this premise is the idea that certain intestinal flora, bifidobacterium in particular, which would be killed off by certain antibiotics, promote the efficacy of immunotherapy...as was noted in this post: Cooties in our gut keep us skinny, smart and cure cancer!?????

Antibiotic
Use May Damper the Efficacy of Checkpoint InhibitorsLisa
Miller, writing for OncLive, Feb 13, 2017.

Use
of antibiotics up to a month before treatment with a checkpoint
inhibitor may decrease the efficacy of the immunotherapy agent,
results of a retrospective analysis show. The analysis, presented
during a presscast of the 2017 Genitourinary Cancers Symposium,
raised suspicion of the relationship between gut microbiota and
antibiotics and their effect on immune checkpoint blockade
agents.

In
patients with metastatic renal cell carcinoma (mRCC), patients who
had received broad-spectrum antibiotics had a shorter median
progression-free survival (PFS) rate when treated with checkpoint
inhibitor immunotherapy than those who had not received antibiotics
of 2.3 versus 8.1 months, respectively.

Previous
preclinical studies using mouse models have suggested an association
between antibiotics and the efficacy of immune checkpoint blockade
agents.2 “This
is the first analysis evaluating the impact of antibiotics on outcome
in mRCC patients treated in the era of immune checkpoint blockade,”
said investigator Lisa Derosa, MD, PhD candidate, of the Gustave
Roussy Cancer Institute, Paris-Sud University in Villejuif,
France.

Researchers analyzed 80 patients with mRCC who were
being treated with checkpoint inhibitors on trials at the Gustave
Roussy institute. Immunotherapy treatments included single-agent
anti–PD-1/PD-L1 therapy (n = 67), a combination of a PD-1 inhibitor
and a CTLA-4 inhibitor (n = 10), and a combination of anti–PD-L1
therapy and bevacizumab (Avastin; n = 3).

A majority of the
enrolled patients were male (65%), 88% had a clear-cell histology,
and 80% of the patients had prior nephrectomy. Twenty-one percent had
favorable disease by International mRCC Database Consortium (IMDC)
risk standards, 57% had intermediate IMDC risk, and 22% had poor-risk
disease. Sixteen patients (20%) had received antibiotics up to 1
month prior to starting treatment with immunotherapy, including
mostly beta-lactamases or fluoroquinolones.

At a median
follow-up of 6 months, overall survival (OS) results were not yet
able to be reached in the overall population, but a negative trend
was already noted for patients who received prior antibiotics. The
objective response rate also favored patients who had not received
antibiotics.

In
a subgroup of 62 patients who were treated with nivolumab (Opdivo)
monotherapy, patients who had not taken antibiotics showed a greater
PFS rate, which also achieved statistical significance.
OS in the nivolumab monotherapy subgroup was also significantly
higher in patients who had not taken recent antibiotics.

“Derosa
shows that antibiotic therapy may have a direct impact on how well
the PD-1 inhibitor nivolumab works in patients with kidney cancer,”
said Sumanta K. Pal, MD, who moderated the presentation.“Immune
based therapies for cancer may have a complex interplay with the
host’s microbiome,” commented Pal, an assistant clinical
professor in the Department of Medical Oncology and Therapeutics
Research and co-director of the Kidney Cancer Program at City of Hope
in Duarte, California. “Antibiotics may influence the bacterial
composition of our gut, and this could in turn impact how effective
immune therapy is.”

Derosa stated that the data was
preliminary but that it encouraged longer follow-up and further
studies to confirm the hypothesis of the study.

“The
observations that Derosa makes have some consistency with preclinical
observation,” Pal said. “We may be able to offer some insights as
to whether or not bacterial composition of the gut could affect
clinical outcomes and that might help us guide antibiotic usage.”
Pal also suggested that these findings are not yet mature enough to
impact clinical practice. The researchers plan to enroll additional
patients in this study to investigate the mechanism of action. Other
studies exploring the relationship between antibiotics and the
efficacy of immunotherapy agents in lung cancer and kidney cancer are
ongoing.